Radioimmunotherapy of peritoneal human colon cancer xenografts with site-specifically modified 212Bi-labeled antibody.
212Bi is a radioisotope that emits highly cytotoxic alpha-particles. alpha-particles have a high linear energy transfer over a short path length. These properties and the 1-h half-life make this isotope suitable for radioimmunotherapy of peritoneal tumors. Therefore, we wanted to test whether monoclonal antibodies labeled with 212Bi would be effective in treating such tumors. We conjugated the antibody B72.3, which is reactive with many human adenocarcinomas, to the chelator linker glycyltyrosyl-lysyl-N-epsilon-diethylenetriaminepentaacetic acid, by reductive amination to the carbohydrate residues of the antibody (J. Rodwell, et al. Proc. Natl. Acad. Sci. USA, 83: 2632-2636, 1986). Athymic nude mice were injected i.p. with LS174T cells, a human colon cancer cell line. Seven to 13 days later the mice were treated with the 212Bi-labeled antibody. We treated the mice using single doses of 180-450 microCi or multiple doses of 80-180 microCi on consecutive days. Dissections were performed 9-16 days after the end of treatment. Both the single and multiple doses resulted in a decrease in tumor burden when compared to tumor from mice receiving unlabeled antibody. Mice in the optimum group showed tumor reductions of greater than 90%. Treatment with a 212Bi-labeled irrelevant antibody was significantly less effective than that with labeled B72.3 antibody. Survival studies showed that mice receiving the labeled antibody had a prolonged survival when compared to control mice.
Simonson
R B
RB
CYTOGEN Corporation, Princeton, New Jersey 08540.
Ultee
M E
ME
Hauler
J A
JA
Alvarez
V L
VL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001729:Bismuth / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000628:therapy; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000401:mortality / Q000628:therapy*; D011868:Radioisotopes / Q000627:therapeutic use*; D015996:Survival Rate; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D001729:Bismuth